Potassium channels show remarkable diversity in their kinetics and voltage dependence, and in their modulation by neurotransmitters and intracellular messengers. Their differential expressions in individual neurons determine to a large extent the firing pattern and duration of action potentials. Since even slight alterations of the action potential duration may have profound effects on the amount of transmitter released from that neuron, potassium channels may be involved in the modulation of synaptic efficacy and plasticity. Indeed, several potassium channels, including the S channel, the A channel and a calcium activated potassium channel, have been implicated as playing key roles in learning. To study the regulation of expression of potassium channel and the possible alterations of potassium channel activities with experience, one would like to study potassium channels molecularly. However, no potassium channels have been purified because of the lack of good assays for their purification. This problem may have been overcome by the cloning of Shaker locus in Drosophila. which was suggested from genetic studies to be a structural gene for a potassium channel, the A channel. Several products are derived from the Shaker locus, probably due to alternative splicing. Of those already characterized, each contains multiple putative membrane spanning regions and an arginine-rich "S4" sequence, homologous to the S4 sequence found in each of the four internally homologous domains of the voltage sensitive sodium channel or calcium channel. These findings raised the following interesting questions concerning the diversity of potassium channels: Do the different Shaker products give rise to A channels of different kinetics or different tissue distribution? Do other potassium channels share enough structural homology with the Shaker products for them to be isolated by cross hybridization? These questions will be approached experimentally in this proposed study.